Publication

Targeting oxidative stress in embryonal rhabdomyosarcoma.

Cancer Cell. 2013 Dec 9;24(6):710-24. doi: 10.1016/j.ccr.2013.11.002.

Abstract

Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS.

Authors

Chen X, Stewart E, Shelat AA, Qu C, Bahrami A, Hatley M, Wu G, Bradley C, McEvoy J, Pappo A, Spunt S, Valentine MB, Valentine V, Krafcik F, Lang WH, Wierdl M, Tsurkan L, Tolleman V, Federico SM, Morton C, Lu C, Ding L, Easton J, Rusch M, Nagahawatte P, Wang J, Parker M, Wei L, Hedlund E, Finkelstein D, Edmonson M, Shurtleff S, Boggs K, Mulder H, Yergeau D, Skapek S, Hawkins DS, Ramirez N, Potter PM, Sandoval JA, Davidoff AM, Mardis ER, Wilson RK, Zhang J, Downing JR, Dyer MA; St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project.